A monoclonal antibody to VLA-4 alpha-chain (CDw49d) induces homotypic lymphocyte aggregation.
The complex processes of cellular adhesion involve a variety of receptor to ligand interactions that are extremely important during the development of immune function. Lymphocyte activation by Ag or mitogen, CTL- and NK-mediated cytolysis, homing to lymphoid-associated tissue, and the attachment of lymphocytes to extracellular matrix proteins are all governed, at least in part, by cell surface adhesion receptors. During the analysis of mAb for the ability to block human cytotoxic T lymphocyte-mediated killing an inhibitory mAb was noted that caused rapid and vigorous aggregation among the CTL. This antibody, mAb L25, also induced aggregation among human T and B tumor cell lines. mAb L25 binds to an epitope on the alpha 4 subunit of the integrin protein VLA-4 and induced an adhesion event requiring divalent cations, energy, a fluid plasma membrane, and an intact cytoskeleton. The Ag-independent homotypic adhesion induced by mAb L25 was not inhibited by mAb to the lymphocyte function associated Ag-1 (CD11a/CD18), CD2, CD4, and CD8, or to their ligands ICAM-1, LFA-3, MHC class I, or MHC class II. We believe that these experiments suggest a role for VLA-4 in a novel system of leukocyte adhesion.
Bednarczyk
J L
JL
Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
McIntyre
B W
BW
D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D002413:Cations, Divalent / Q000494:pharmacology; D002414:Cations, Monovalent / Q000494:pharmacology; D002448:Cell Adhesion; D002449:Cell Aggregation; D006801:Humans; D066298:In Vitro Techniques; D039001:Integrin alpha Chains; D016029:Receptors, Very Late Antigen / Q000276:immunology / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C063493:CDw49d; D002413:Cations, Divalent; D002414:Cations, Monovalent; D039001:Integrin alpha Chains; D016029:Receptors, Very Late Antigen; D013755:Tetradecanoylphorbol Acetate